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Health-AIDS: Gene therapy in mice opens up new front against AIDS

Agence France-Presse - December 21, 2000 click here for portuguese language version click here for francais language version click here for espanol language version

PARIS, Dec 21 (AFP) - French doctors said Thursday they had devised a gene therapy in mice that dealt a blow to the AIDS virus by fooling it into latching on to a passing protein rather than a cell, causing it to wither and die for lack of nutrition.

The research by doctors at Edouard-Herriot Hospital in Lyons, one of France's top institutions in medical innovation, is published Friday in the US magazine AIDS.

Researcher Kamel Sanhadji told AFP that the work had been carried out on mice that had been genetically modified to be without immune defences, to enable the rodents to receive human cells yet not reject them.

Two genes were then inserted into the mice, causing them to produce a substance called glycoprotein.

This circulated in the blood, mimicking CD4 receptors, the part of a cell surface to which the human immunodeficiency virus (HIV) is attracted.

"When the AIDS virus meets a human cell, it latches on to its CD4 receptors and then infiltrates the cell," Sanhadji said.

"We sought to imitate this process by placing receptors in the vicinity of the virus, but in a soluble form."

The mice were infected with HIV a week after the gene transfer, but the virus was fooled by the false CD4s and did not penetrate cells, which meant that it was deprived of an energy source to survive and reproduce, Sanhadji said.

After three weeks, "virus levels in the blood were quite undetectable, even using the most powerful techniques, such as gene amplification," he said.

He added, however, that it was too early to say whether the virus may be holing up in a reservoir of the body, such as the lymph glands, the brain or spinal cord.

The next step will be test the therapy on primates, with the hope that if all goes well, trials could be carried out on humans "two or three years from now," starting with people who have resistance to the anti-retroviral cocktail of AIDS drugs.

One of the challenges will be to find a way of delivering the therapy to humans, using a disabled virus with the gene tucked inside as a Trojan Horse, infecting each of the body's cells and changing its DNA programming accordingly.

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